인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
DBpia AI
AI 에이전트
AI 아이디어
AI 리더
AI 뷰어
Citeasy
크롬 서지관리 다운로드
지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록·키워드
Genetic information in cells flows from DNA to RNA to proteins, which form molecular machines. During normal ageing, cell intrinsic and environmental factors alter this flow of information by damaging DNA in cells, including postmitotic neurons. Damage to DNA is associated with age-related neurodegenerative diseases such as Alzheimer's disease (AD). We previously reported an increase in DNA repair mechanisms in a fly model of AD. However, the causal mechanisms underlying somatic mutations in AD remain unclear. Here, we combine in silico methods from single-cell genomics of patients with AD with experimental validation in a Drosophila model of AD to elucidate the DNA repair processes in AD. We show that the levels of poly(ADP‒ribose) polymerase 1 (PARP1), which mediates multiple DNA damage repair pathways, are increased in the brains of patients with AD. We found that higher PARP1 levels in neurons from patients with AD are linked to increased disease risk and a greater burden of somatic mutations. Nucleotide imbalance can increase the frequency of somatic mutations upon activation of DNA repair processes. Using a fly model of AD, we identified a metabolic signature in AD animals characterised by decreased levels of phosphorylated nucleotides. Enhancing nucleotide metabolism via dietary supplementation or genetic manipulation protects against AD pathology in animals. Finally, Mendelian randomisation revealed that higher expression of human deoxyguanosine kinase (DGUOK) is linked to a lower risk of developing AD. Our results suggest that enhancing nucleotide metabolism could improve DNA repair and serve as an adjunct therapy to delay AD progression.
인공지능 문자 인식 모델을 통해 추출된 텍스트로, 일부 오타나 오류가 포함될 수 있으나 지속적으로 개선 중입니다.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
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